The DOI matches its Crossref record; 150 of the 150 references it cites were found in a registry or an index.
Circular RNAs: Biogenesis, Function, and a Role as Possible Cancer Biomarkers
Open accessAbstract
Circular RNAs (circRNAs) are a class of noncoding RNAs (ncRNAs) that form covalently closed continuous loop structures, lacking the terminal 5 ′ and 3 ′ ends. CircRNAs are generated in the process of back-splicing and can originate from different genomic regions. Their unique circular structure makes circRNAs more stable than linear RNAs. In addition, they also display insensitivity to ribonuclease activity. Generally, circRNAs function as microRNA (miRNA) sponges and have a regulatory role in transcription and translation. They may be also translated in a cap-independent manner in vivo, to generate specific proteins. In the last decade, next-generation sequencing techniques, especially RNA-seq, have revealed great abundance and also dysregulation of many circRNAs in various diseases, suggesting their involvement in disease development and progression. Regarding their high stability and relatively specific differential expression patterns in tissues and extracellular environment (e.g., body fluids), they are regarded as promising novel biomarkers in cancer. Therefore, we focus this review on describing circRNA biogenesis, function, and involvement in human cancer development and address the potential of circRNAs to be effectively used as novel cancer diagnostic and prognostic biomarkers.
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![Figure 1 Schematic representation of circRNA biogenesis. (a) Canonical pre-mRNA splicing, yielding a mature mRNA molecule. (b) Lariat-driven circularization (exon skipping). Following canonical splicing, exons in exon-containing lariats undergo back-splicing and circularization, which results in the formation of ecircRNA or EIciRNA molecules. (c) Intron pairing-driven circularization, utilizing coupling of flanking introns by direct base pairing between cis-acting regulatory elements that contain reverse complementary sequences (e.g., Alu repeats). Intron pairing is followed by back-splicing and exon circularization. (d) CircRNA biogenesis, mediated by trans-acting factors, such as RNA-binding proteins (RBPs) (e.g., QKI, MBL/MBNL1) that bind to specific sequence motifs of flanking introns on linear pre-mRNA, dimerize, and facilitate back-splicing and exon circularization. (e) Regulation of circRNA biogenesis by the RNA-editing enzyme ADAR. ADAR destabilizes intron base pairing interactions through the action of adenosine-to-inosine (A-to-I) editing, which impairs pre-mRNA looping and diminishes exon circularization. (f) Resplicing-driven circularization. EcircRNAs may be formed from mature mRNA exons that undergo back-splicing and circularization. (g) Formation of ciRNAs from intron lariats that escape the usual intron debranching and degradation, following the canonical pre-mRNA splicing. (h) Formation of intergenic circRNAs. This figure is adapted from Wang et al. [151].](/paper-figures/f737a9939afe4c49bf92060003f458d7/circular-rnas-biogenesis-function-and-a-role-as-possible-cancer-biomarkers-figure-1.jpg)
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“Originating from various genomic regions, circRNAs are synthesized by the back-splicing of protein-coding precursor mRNAs (primarily in eukaryotes) [25,26].”
From Circular RNAs in depression: Biogenesis, function, expression, and therapeutic potential (2021) · cites this paper as [26]
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6 retracted
circRNA_100290 plays a role in oral cancer by functioning as a sponge of the miR-29 family
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Additional file 1 of Circular RNA expression profile in blood according to ischemic stroke etiology
Ostolaza, A., Blanco‐Luquin, I., Urdánoz‐Casado, A., Rubio, I., Labarga, A., Zandio, B., Roldán, M., Martínez-Cascales, J., Mayor, S., Herrera, M., et al. (2020) · Figshare · doi:10.6084/m9.figshare.11967198
Liu, S., Wang, Y., Wang, T., Shi, K., Fan, S., Li, C., Chen, R., Wang, J., Jiang, W., Zhang, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26682055
Liu, S., Wang, Y., Wang, T., Shi, K., Fan, S., Li, C., Chen, R., Wang, J., Jiang, W., Zhang, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26682034
Ma, S., Xu, Y., Qin, X., Tao, M., Gu, X., Shen, L., Chen, Y., Zheng, M., Qin, S., Wu, G., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26157269
Liu, S., Wang, Y., Wang, T., Shi, K., Fan, S., Li, C., Chen, R., Wang, J., Jiang, W., Zhang, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26682040
Liu, S., Wang, Y., Wang, T., Shi, K., Fan, S., Li, C., Chen, R., Wang, J., Jiang, W., Zhang, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26682049
Liu, S., Wang, Y., Wang, T., Shi, K., Fan, S., Li, C., Chen, R., Wang, J., Jiang, W., Zhang, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26682052
Liu, S., Wang, Y., Wang, T., Shi, K., Fan, S., Li, C., Chen, R., Wang, J., Jiang, W., Zhang, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26682043
Additional file 2 of Circular RNA expression profile in blood according to ischemic stroke etiology
Ostolaza, A., Blanco‐Luquin, I., Urdánoz‐Casado, A., Rubio, I., Labarga, A., Zandio, B., Roldán, M., Martínez-Cascales, J., Mayor, S., Herrera, M., et al. (2020) · Figshare · doi:10.6084/m9.figshare.11967207
Liu, S., Wang, Y., Wang, T., Shi, K., Fan, S., Li, C., Chen, R., Wang, J., Jiang, W., Zhang, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26682046
Liu, S., Wang, Y., Wang, T., Shi, K., Fan, S., Li, C., Chen, R., Wang, J., Jiang, W., Zhang, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26682028
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Circular RNAs at the crossroads of oxidative stress: novel targets for precision therapeutics
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“CircRNA biogenesis generates three principal structural classes: exonic circRNAs (ecircRNAs), intronic circRNAs (ciRNAs), and exon–intron circRNAs (EIciRNAs) (Bolha et al., 2017).”
Metadata
- Authors
- Bolha, L., Ravnik-Glavač, M., & Glavač, D.
- Affiliations
- University of Ljubljana (SI)
- Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Corresponding author
- Glavač, Damjan
- Venue
- International Journal of Genomics
- Publisher
- Wiley
- Published
- 2017
- Volume
- 2017
- Pages
- 1-19
- ISSN
- 2314-436X (ISSN-L)
- 2314-4378
- PMC
- PMC5733622
- OpenAlex
- W2771561127
- Cited by
- 166
- References
- 150
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 22 · 2023: 17 · 2022: 21 · 2021: 21 · 2020: 38 · 2019: 20 · 2018: 15
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- International Journal of Genomics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- circular RNA, circRNA biogenesis, back-splicing, non-coding RNA, microRNA sponge, cap-independent translation, circRNA stability, tumor markers, cancer diagnosis, cancer prognosis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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